The Program includes 27 members from 8 basic and clinical departments within Duke University. Total funding for program members is $21,313,013, of which $13,716,487 is from peer- reviewed sources. A cancer focus is illustrated by $9,448,240 or 68.9% of funding from the NCI, the American Cancer Society or the Department of Defense. From 2004-2008, program members published 628 papers in peer-reviewed journals cited in PubMed. Of these publications, 6% are the result of intra-programmatic collaborations and 33% due to inter-programmatic collaborations.The scientific goals of the Program are to 1) conduct basic, translational and clinical research to elucidate mechanisms of action and of resistance of cancer therapies that target cellular and molecular abnormalities and cell signaling pathways; 2) identify biomarkers, pharmacokinetic/pharmacodynamic endpoints, and molecular and functional imaging parameters that correlate with the anti-tumor activity of cancer therapies and 3) develop innovative methods and strategies for optimized delivery of cancer therapeutics, specifically, small molecules, gene therapy and biologies, 4) design and conduct innovative clinical trials of novel and current therapies that incorporate knowledge of of drug action and resistance, biomarkers, endpoints of response, and advances in pharmacogenomics and pharmacogenetics, and 5) conduct eariy phase discovery, evaluation and optimization of small molecule therapeutics directed against novel therapeutic targets and pathways deregulated in cancer. The organizational goals of the Program are to provide an infrastructure to facilitate the discovery and evaluation of new cancer therapies, enhance pursuit of individual research programs of program members, and facilitate intra- and inter-programmatic collaborative research activities in the area of cancer therapeutics. This will include the organization of retreats, seminar series and related program activities to facilitate interaction and exchange of ideas and information between programs and program members. A major programmatic goal is to promote and enhance training of graduate students, post-doctoral fellows and physician-scientists in basic, translational and clinical sciences relevant to cancer therapeutics. The structure of the program represents a continuum of research activities from the bench to the clinic that provides an ideal environment and opportunity to conduct translational research in an iterative process involving testing findings from the laboratory into hypothesis-driven mechanistic clinical trials, that can generate new questions to be addressed in the laboratory, thereby constantly refining and honing hypotheses that can lead to more effective therapies for cancer.